The mixed leukocyte culture (MLC) of peripheral blood lymphocytes (PBL) prospective kidney transplant recipients and their respective donors produces a primed cell population that functions as suppressors. The primed cells suppress the primary and secondary MLC when added as third components, without demonstrable cytotoxic cells. Suppressor cells are derived from the MLC's of related pairs that were genotyped to be: (1) serologically defined (SD) identical and lymphocyte-defined (LD) non-identical, and (2) HLA (total MHC) identical. Primed cells derived from MLC of unrelated HLA non-identical individuals also show similar effects. Two general patterns of inhibition are observed; a marked specific suppression of the autologous respondng cells and to a lesser degree, nonspecific suppression. The T cell fraction derived from the primed suppressor population is suppressive, the cells with B cell characteristics are not suppressive. The suppressive effect of cells generated in MLC is being serially monitored after kidney transplantation. The suppressive activity of the primed cells appear to be absent in the postoperative period (4 weeks), perhaps due to high dose immunosuppression, but later in the course suppression is evident again (2-5 months). Manipulation of this T suppressor cell population may prove to be of value in enhancing graft acceptance.